A randomised, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of ropinirole for 26 weeks and to further evaluate the incidence of augmentation and rebound for a further 40 weeks open-label extension treatment period in subjects suffering from moderate to severe Restless Legs Syndrome

Phase 1

• Conditions: Restless Legs Syndrome (RLS)

• Registration Number: EUCTR2005-005372-32-ES
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2006-02-02
• Study Completion: 2008-09-11
• Last Update Posted: 7 September 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 0

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply at the time of entry into the double-blind phase:
1. Male and female subjects, = 18 years and < 80 years of age.
A female is eligible to enter and participate in the study if she is of:
a) Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
b) Childbearing potential, has a negative result on all required pregnancy tests prior to randomisation, and agrees to an acceptable contraceptive method.
2. Subjects with a diagnosis of idiopathic RLS using the RLS Diagnostic Clinical Interview and the International RLS Study Group (IRLSSG) Diagnostic Criteria during the Screening Visit.
3. Subjects have had RLS symptoms with a history of a minimum of 15 RLS episodes during the previous month. If this is not possible due to the subject being on previous medication to treat RLS the investigator should ensure that the subject should have experienced 4-5 episodes of RLS symptoms during the last 7 days of the wash-out phase (see below). The subject must discontinue and wash-out any previous medication for the treatment of RLS or sleep prior to the Baseline Visit (Day 0). The minimum discontinuation period for wash-out is generally 5 half-lives of the medication or 7 consecutive evenings/nights medication-free prior to baseline, whichever is the longer period.
4. During the Wash-out and Screening Phase, RLS symptoms must be present for at least 4 of the last 7 nights immediately prior to the Baseline Visit (e.g., any combination of evenings and /or nights for = 4 days).
5. Subjects with a total score = 24 on the IRLS Rating Scale at baseline (Day 0).
6. Subjects with RLS symptoms that cause significant sleep impairment based on clinical judgment and guided by subject response to Question 4 of the IRLS Rating Scale (e.g., ordinarily this will include a response of (3) severe or (4) very severe sleep disturbance) at the Baseline Visit OR RLS symptoms that cause severe/very severe discomfort in the limbs based on clinical judgment and guided by subject response to Question 1 of the IRLS Rating Scale (e.g., this will include a response of (3) severe or (4) very severe discomfort in limbs) at the Baseline Visit (Day 0).
7. Subjects must be experiencing RLS symptoms requiring treatment at night-time.
8. Subjects must have given written informed consent prior to any specific study procedures.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria applies:
1. Subjects suffering from augmentation and/ or ‘end of treatment’ rebound RLS symptoms at baseline (Day 0). Augmentation is defined as RLS symptoms that occurred while on treatment and occur earlier in the afternoon/evening than they did before, symptoms which are more severe than when not treated, symptoms which start after less time at rest than they did before treatment, or symptoms which involve other parts of the body, such as the arms or trunk. ‘End of treatment’ rebound describes worsening of symptoms from baseline that occur after pharmacological treatment is stopped.
2. Subjects with a previous history of augmentation.
3. Subjects who have exhibited intolerance to ropinirole or any other dopamine agonist.
4. Subjects requiring treatment of daytime RLS symptoms (daytime defined as 10:00 hours until 17:00 hours).
5. Signs of secondary RLS (e.g., end stage renal disease, iron deficient anaemia or pregnancy at Baseline Visit).
6. Subjects with a serum ferritin level of < 10 mcg/L (ng/mL) at Screening Visit.
7. Subjects who suffer from a primary sleep disorder other than RLS that may significantly affect the symptoms of RLS (e.g. narcolepsy, sleep terror disorder, sleepwalking disorder, breathing related sleep disorder).
8. Subjects diagnosed with movement disorders (e.g., Parkinson’s Disease, dyskinesias, and dystonias).
9. Subjects who have medical conditions which could affect efficacy assessments or clinically significant or unstable medical conditions that present a safety concern. These may include, but are not limited to, the following disorders: diabetes, peripheral neuropathy, rheumatoid arthritis, fibromyalgia syndrome, symptomatic orthostatic hypotension, severe cardiovascular disease, hepatic or renal failure, pleuro-pulmonary fibrosis, major psychotic illness.
10. Subjects having a clinically significant abnormal laboratory value, ECG, or physical examination findings not resolved by the time of the baseline examinations (Day 0). Abnormal 12-lead ECG findings include, but are not limited to, the following: myocardial ischemia, clinically significant conduction abnormalities, or clinically significant arrhythmias.
11. Subjects with a diastolic blood pressure = 110mmHg or = 50mmHg or systolic blood pressure = 180mmHg or = 90mmHg at the Screening or Baseline Visit.
12. Subjects with a history of alcohol or substance abuse within the past year.
13. Subjects taking any medication known to induce drowsiness, affect RLS or sleep and which have not been discontinued prior to the Baseline Visit. These medications include the following:
Atypical and typical antipsychotics, anticonvulsants, opioids (including propoxyphene and oxycodone), anxiolytics, all sedatives/hypnotics (including benzodiazepines), lithium, oral neuroloeptics, stimulants (including methylphenidate), dopamine agonists (including ropinirole), dopamine antagonists (e.g., typical neuroleptics, metoclopromide), levodopa/carbidopa, clonidine, and sedating antihistamines (e.g., chlorpheniramine, diphenhydramine, hydroxyzine) or any preparations containing these antihistamines.
The minimum discontinuation period is generally 5 half lives or 7 consecutive evenings/nights medication free, prior to baseline, whichever is the longer period. Exceptions to this general rule are: fluoxetine, monoamine oxidase inhibitors: 4 weeks.
For subjects entering the

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified